B-ALLPhase 1NCT04088890
Autologous CD22 CAR T Cells in Adults w/ Recurrent or Refractory B Cell Malignancies
A Phase 1 study testing Fludarabine, Cyclophosphamide and CD22 CAR in people with B-ALL and B-cell Non Hodgkin Lymphoma, run by Matthew Frank at 1 site in United States.
Trial summary
The primary purpose of this study is to test whether CD22-CAR T cells can be successfully made from immune cells collected from adults with relapsed/refractory B-cell malignancies (leukemia and lymphoma). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- B-ALL, B-cell Non Hodgkin Lymphoma, DLBCL
- What is being tested?
- Fludarabine, Cyclophosphamide and CD22 CAR
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Sep 2019to 7 Mar 2025
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Disease Status
- Disease Status of ALL
- Must have chemotherapy refractory disease defined as progression or stable disease after two lines of therapies, or relapsed disease after achieving CR.
- Subjects with persistent or relapsed minimal residual disease (MRD) (by flow cytometry, PCR, FISH, or next generation sequencing) require verification of MRD on two occasions at least 2 weeks apart.
- Subjects with Philadelphia Chromosome positive acute lymphoblastic leukemia (Ph+ALL) are eligible if they progressed, had stable disease or relapsed after two lines of therapy, including tyrosine kinase inhibitors (TKIs).
- Subjects with recurrence of isolated CNS relapse after achieving complete remission (CR) are eligible.
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- Disease Status of aggressive B-cell NHL •Histologically confirmed aggressive B cell NHL including the following types defined by WHO 2008: oDLBCL not otherwise specified; T cell/histiocyte rich large B cell lymphoma; DLBCL associated with chronic inflammation; Epstein Barr virus (EBV)+ DLBCL of the elderly; OR oprimary mediastinal (thymic) large B cell lymphoma; OR otransformation of follicular lymphoma, marginal zone lymphoma or chronic lymphocytic leukemia/small lymphocytic lymphoma to DLBCL; OR oFollicular Lymphoma Grade 3B •Subjects with DLBCL, Follicular Lymphoma Grade 3B -or-
- Subjects with transformed FL, MZL, or CLL/SLL who HAVE NOT received chemotherapy prior to transformation:
- oMust have received an anthracycline regimen and an anti CD20 monoclonal antibody (unless documented CD20-negative) and be refractory or relapsed after second line of DLBCL treatment. Subjects with a partial response to second line therapy must be ineligible for autologous transplant.
- •Subjects with transformed FL, MZL, or CLL/SLL who HAVE received anthracycline-containing chemotherapy prior to transformation: oMust have progressed, had SD or recurred with transformed disease after initial treatment for DLBCL.
- Measureable Disease
- Subjects with ALL: must have evaluable or measurable disease (MRD positive by flow cytometry, NGS, or PCR is acceptable).
- Subjects with aggressive B-cell NHL: must have evaluable or measurable disease according to the revised IWG Response Criteria for Malignant Lymphoma[38]. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy.
- CD22 expression
- •Subjects with ALL: CD22 positive expression on malignant cells is required and must be detected by immunohistochemistry or flow cytometry. The choice of whether to use flow cytometry or immunohistochemistry will be determined by what is the most easily available tissue sample in each subject.
- CD22 expression must be demonstrated subsequent to any anti-CD22 targeted therapy (e.g. Moxetumomab pasudotox or inotuzumab ogozamicin) in subjects with ALL.
- •Subjects with aggressive B-cell NHL: CD22 expression at any level, including undetectable, will be acceptable. Subjects must have archival tissue available for analysis of CD22 expression or must be willing to undergo a biopsy of easily accessible disease.
- Prior Bone Marrow-Stem Cell Transplant Subjects who have undergone autologous SCT with disease progression or relapse following SCT are eligible. Subjects who have undergone allogeneic SCT will be eligible if, in addition to meeting other eligibility criteria, they have no evidence of GVHD and have been without immunosuppressive agents for at least 30 days.
- Prior Therapy Wash-out At least 2 weeks or 5 half lives, whichever is shorter, must have elapsed since any prior systemic therapy at the time the subject is planned for leukapheresis, except for systemic inhibitory/stimulatory immune checkpoint therapy, which requires 5 half lives.
- Exceptions:
- There is no time restriction with regard to prior intrathecal chemotherapy provided there is complete recovery from any acute toxic effects of such;
- Subjects receiving hydroxyurea may be enrolled provided there has been no increase in dose for at least 2 weeks prior to starting apheresis;
- Subjects who are on standard ALL maintenance type chemotherapy (vincristine, 6-mercaptopurine or oral methotrexate) may be enrolled provided that chemotherapy is discontinued at least 1 week or 5 half lives, whichever is shorter, prior to apheresis.
- Subjects receiving steroid therapy at physiologic replacement doses only are allowed provided there has been no increase in dose for at least 2 weeks prior to starting apheresis;
- For radiation therapy: Radiation therapy must have been completed at least 3 weeks prior to apheresis, with the exception that there is no time restriction if the volume of bone marrow treated is less than 10% and also the subject has measurable/evaluable disease outside the radiation port or the site of radiation has documented progression.
- Prior CAR Therapy Subjects who have undergone prior CAR therapy must be at least 30 day post CAR infusion and have < 5% of CD3+ cells express the previous CAR if a validated assay is available.
- Toxicities due to prior therapy must be stable or resolved (except for clinically non significant toxicities such as alopecia or cytopenias covered in *footnote to #10)
- Age greater than or equal to 18 years of age
- Eastern cooperative oncology group (ECOG) performance status of 0, 1, or 2; or Karnofsky ≥ 60% (See section 13.1, Appendix A)
- Normal Organ and Marrow Function (supportive care is allowed per institutional standards, i.e. filgrastim, transfusion)
- ANC ≥ 750/uL*
- Platelet count ≥ 50,000/uL*
- Absolute lymphocyte count (ALC) ≥ 150/uL*
- Adequate renal, hepatic, pulmonary and cardiac function defined as:
- Creatinine ≤ 2 mg/dL OR creatinine clearance ≥ 60 mL/min
- Serum ALT/AST ≤ 10x Upper limit of normal (ULN) (Elevated ALT/AST related to leukemia involvement of the liver will not disqualify a subject).
- Total bilirubin ≤ 1.5 mg/dL, except in subjects with Gilbert's syndrome.
- Cardiac ejection fraction ≥ 45%, no evidence of physiologically significant pericardial effusion as determined by an ECHO, MUGA or Cardiac MRI [performed within 180 days or after most recent anthracycline based treatment or mediastinal radiation therapy (whichever is most recent)]
- No clinically significant ECG findings
- No clinically significant pleural effusion
- Baseline O2 saturation > 92% on room air * ALL subjects will not be excluded because of pancytopenia ≥ Grade 3 if it is felt by the investigator to be due to underlying leukemia.
- CNS Status Subjects with CNS involvement are eligible as long as there are no overt signs or symptoms that in the evaluation of the investigator would mask or interfere with the neurological assessment of toxicity.
- Females of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to leukapheresis(females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential)
- Contraception Subjects of child bearing or child fathering potential must be willing to practice birth control from the time of enrollment on this study and for four (4) months after receiving the preparative lymphodepletion regimen.
- Ability to give informed consent. Must be able to give informed consent. Legal authorized representative (LAR) is permitted if subject is cognitively able to provide verbal assent.
Who cannot join
- Recurrent or refractory ALL limited to isolated testicular disease.
- Hyperleukocytosis (≥ 50,000 blasts/μL) or rapidly progressive disease that in the estimation of the investigator and sponsor would compromise ability to complete study therapy.
- History of other malignancy, unless disease free for at least 3 years. At the discretion of the Principal Investigator, subjects in remission for 1-2 years prior to enrollment may be deemed eligible after considering the nature of other malignancy, likelihood of recurrence during one year following CAR therapy, and impact of prior treatment on risk of CD22-CAR T cells. Subjects in remission <1 year are not eligible.
- Exception: Nonmelanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) is eligible.
- Hormonal therapy in subjects in remission > 1 year will be allowed.
- Presence of active fungal, bacterial, viral, or other infection requiring intravenous antimicrobials. Simple UTI and uncomplicated bacterial pharyngitis are permitted if responding to active treatment.
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- No knowledge of:
- HIV,
- Hepatitis B (HBsAg positive) or
- Hepatitis C virus (anti HCV positive) infection. A history of hepatitis B or hepatitis C is permitted if the viral load is undetectable per quantitative PCR and/or nucleic acid testing.
- Presence of cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement that in the judgment of the investigator may impair the ability to evaluate neurotoxicity.
- History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment.
- Any medical condition that in the judgement of the sponsor investigator is likely to interfere with assessment of safety or efficacy of study treatment.
- History of severe immediate hypersensitivity reaction to any of the agents used in this study.
- Women who are pregnant or breastfeeding.
- In the investigator's judgment, the subject is unlikely to complete all protocol required study visits or procedures, including follow up visits, or comply with the study requirements for participation.
- Primary immunodeficiency or history of autoimmune disease (e.g. Crohns, rheumatoid arthritis, systemic lupus) requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase I/Ib Clinical Trial of Autologous CD22 Chimeric Antigen Receptor (CAR) T Cells in Adults With Recurrent or Refractory B Cell Malignancies
The primary purpose of this study is to test whether CD22-CAR T cells can be successfully made from immune cells collected from adults with relapsed/refractory B-cell malignancies (leukemia and lymphoma).
Read the detailed description
Primary Objective:
- Determine the feasibility of manufacturing CD22 CAR T cells using the Miltenyi CliniMACS Prodigy® system for administration to adults with relapsed/refractory CD22 expressing B-cell ALL or relapsed/refractory aggressive B-cell non hodgkins lymphoma (NHL).
- Establish the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of CD22 CAR T cells in adults with relapsed/refractory aggressive B-cell NHL.
- Determine the safety of an established dose of CD22-CAR T cells in adults with relapsed/refractory CD22 expressing B-cell ALL and the safety of the MTD/RP2D of CD22-CAR T cells in adults with relapsed/refractory aggressive B-cell NHL.
Secondary Objective:
- Assess the clinical activity of CD22-CAR T cells in adults with R/R CD22 expressing B-cell ALL and R/R aggressive B-cell NHL, including overall survival (OS) and progressive free survival (PFS).
- Being tested
- Fludarabine, Cyclophosphamide, CD22 CAR
- Keywords
- CD22, CAR T cells
- Medical subject headings
- Lymphoma, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FludarabineDrug
Fludarabine 30 mg/m2
CyclophosphamideDrug
Cyclophosphamide 500 mg/m2
CD22 CARDrug
Autologous T cells transduced with lentiviral vector (CD22.BB.Z) Chimeric Antigen Receptor (CD22 CAR). Autologous CD22 CAR T cells will be administered intravenously at Dose Level 1 in subjects with ALL. Autologous CD22-CAR T cells will be administered in 3 escalating doses (Dose Level 1, 2, and 3) in subjects with aggressive B-cell NHL to determine MTD/RP2D
| Study group | Role | What they receive |
|---|---|---|
| R/R ALL | Experimental | Relapsed/refractory ALL
Lymphodepletion prior to CD22 CAR T cell infusion (Day 0) will occur as follows:
* Fludarabine 30 mg/m2 per day IV for days 5, 4, 3
* Cyclophosphamide 500 mg/m2 per day IV for days 5, 4, 3
Autologous CD22 CAR T cells will be administered intravenously at Dose1: 3 x 10^5cells/kg (± 20%) 10 Receives: Drug: Fludarabine; Drug: Cyclophosphamide; Drug: CD22 CAR |
| R/R aggressive B-cell NHL | Experimental | Relapsed/refractory aggressive B-cell non-Hodgkin lymphoma.
Lymphodepletion prior to CD22 CAR T cell infusion (Day 0) will occur as follows:
* Fludarabine 30 mg/m2 per day IV for days 5, 4, 3
* Cyclophosphamide 500 mg/m2 per day IV for days 5, 4, 3
Autologous CD22-CAR T cells will be administered in 3 escalating doses (Dose Level 1, 2, and 3) to determine MTD/RP2D.
Dose1: 1 x 10^6 cells/kg (± 20%) Dose2: 3 x 10^6 cells/kg (± 20%) Dose3: 1 x 10^7 cells/kg (± 20%) Receives: Drug: Fludarabine; Drug: Cyclophosphamide; Drug: CD22 CAR |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of Successful Manufacture of CD22 CAR T Cells
The percentage of apheresis samples (fresh or frozen) that are successfully processed and expanded to manufacture CD22 CAR T cells will be determined for each dose cohort.
Measured: 7-11 days from start of manufacturing
Incidence of Dose Limiting Toxicities (DLTs) in Subjects With Aggressive B-cell NHL
Incidence and severity of dose limiting toxicities (DLTs) following chemotherapy preparative regimen and infusion of CD22 CAR T cells, as recorded and graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, at each dose level tested in subjects with aggressive B-cell NHL
Measured: 28 days after infusion
Safety Evaluation of CD22-CAR T Cells in Subjects With ALL
Incidence and severity of dose limiting toxicities (DLTs) following chemotherapy preparative regimen and infusion of CD22 CAR T cells, as recorded and graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, at each dose level tested in subjects with ALL
Measured: 28 days after infusion
Secondary outcomes (2)
Clinical Activity of CD22-CAR T Cells in Adults With Relapsed/Refractory CD22-expressing B-cell ALL at Target Dose
Clinical response was assessed at Day 28 per modified International Working Group (IWG) criteria for acute lymphoblastic leukemia. Complete Response (CR) was defined as <5% bone marrow blasts with hematologic recovery. CR with minimal residual disease (MRD-) required no detectable MRD by protocol-specified assay, whereas CR with MRD+ indicated detectable MRD. Progressive Disease (PD) was defined as increased bone marrow blasts or clinical progression.
Measured: 28 days after infusion
Clinical Activity of CD22-CAR T Cells in Adults With Relapsed/Refractory Aggressive B-cell NHL at MTD/RP2D
Clinical response was assessed at Month 3 per Lugano 2014 criteria for non-Hodgkin lymphoma. Complete Response (CR) was defined as disappearance of all evidence of disease. Partial Response (PR) was defined as ≥50% reduction in measurable disease. Stable Disease (SD) was defined as neither sufficient shrinkage for PR nor sufficient increase for PD. Progressive Disease (PD) was defined as appearance of new lesions or ≥50% increase in disease burden.
Measured: 3 months after infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2019
- Study start12 Sep 2019
- Primary completion7 Nov 2024
- Study completion7 Mar 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for B-ALLStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- Matthew Frank
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), The Leukemia and Lymphoma Society, American Society of Hematology
- Responsible party
- Sponsor-investigator, Matthew Frank, Stanford University
- Investigators
- Matthew Frank, MD, PhD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04088890
- Sponsor's protocol ID
- IRB-50836
- Other IDs
- NCI-2019-06810, 5K08CA248968-05
- Status last verified
- Mar 2026
- First submitted
- 11 Sep 2019
- Last updated
- 30 Mar 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Frank MJ, Baird JH, Kramer AM, Srinagesh HK, Patel S, Brown AK, Oak JS, Younes SF, Natkunam Y, Hamilton MP, Su YJ, Agarwal N, Chinnasamy H, Egeler E, Mavroukakis S, Feldman SA, Sahaf B, Mackall CL, Muffly L, Miklos DB; CARdinal-22 Investigator group. CD22-directed CAR T-cell therapy for large B-cell lymphomas progressing after CD19-directed CAR T-cell therapy: a dose-finding phase 1 study. Lancet. 2024 Jul 27;404(10450):353-363. doi: 10.1016/S0140-6736(24)00746-3. Epub 2024 Jul 9.
PubMed 38996463Baird JH, Frank MJ, Craig J, Patel S, Spiegel JY, Sahaf B, Oak JS, Younes SF, Ozawa MG, Yang E, Natkunam Y, Tamaresis J, Ehlinger Z, Reynolds WD, Arai S, Johnston L, Lowsky R, Meyer E, Negrin RS, Rezvani AR, Shiraz P, Sidana S, Weng WK, Davis KL, Ramakrishna S, Schultz L, Mullins C, Jacob A, Kirsch I, Feldman SA, Mackall CL, Miklos DB, Muffly L. CD22-directed CAR T-cell therapy induces complete remissions in CD19-directed CAR-refractory large B-cell lymphoma. Blood. 2021 Apr 29;137(17):2321-2325. doi: 10.1182/blood.2020009432.
PubMed 33512414
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/Ib Clinical Trial of Autologous CD22 Chimeric Antigen Receptor (CAR) T Cells in Adults With Recurrent or Refractory B Cell Malignancies
- ClinicalTrials.gov ID
- NCT04088890
- Acronym / sponsor ID
- IRB-50836
- Keywords
- CD22, CAR T cells
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- Matthew FrankUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), The Leukemia and Lymphoma Society, American Society of Hematology
- Study start
- 12 Sep 2019 (actual)
- Primary completion
- 7 Nov 2024 (actual)
- Study completion
- 7 Mar 2025 (actual)
- First posted
- 13 Sep 2019 (actual)
- Results
- Posted 30 Mar 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary purpose of this study is to test whether CD22-CAR T cells can be successfully made from immune cells collected from adults with relapsed/refractory B-cell malignancies (leukemia and lymphoma).
Detailed description
Primary Objective:
- Determine the feasibility of manufacturing CD22 CAR T cells using the Miltenyi CliniMACS Prodigy® system for administration to adults with relapsed/refractory CD22 expressing B-cell ALL or relapsed/refractory aggressive B-cell non hodgkins lymphoma (NHL).
- Establish the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of CD22 CAR T cells in adults with relapsed/refractory aggressive B-cell NHL.
- Determine the safety of an established dose of CD22-CAR T cells in adults with relapsed/refractory CD22 expressing B-cell ALL and the safety of the MTD/RP2D of CD22-CAR T cells in adults with relapsed/refractory aggressive B-cell NHL.
Secondary Objective:
- Assess the clinical activity of CD22-CAR T cells in adults with R/R CD22 expressing B-cell ALL and R/R aggressive B-cell NHL, including overall survival (OS) and progressive free survival (PFS).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| R/R ALL | Experimental | Drug: Fludarabine, Drug: Cyclophosphamide, Drug: CD22 CARRelapsed/refractory ALL Lymphodepletion prior to CD22 CAR T cell infusion (Day 0) will occur as follows: * Fludarabine 30 mg/m2 per day IV for days 5, 4, 3 * Cyclophosphamide 500 mg/m2 per day IV for days 5, 4, 3 Autologous CD22 CAR T cells will be administered intravenously at Dose1: 3 x 10^5cells/kg (± 20%) 10 |
| R/R aggressive B-cell NHL | Experimental | Drug: Fludarabine, Drug: Cyclophosphamide, Drug: CD22 CARRelapsed/refractory aggressive B-cell non-Hodgkin lymphoma. Lymphodepletion prior to CD22 CAR T cell infusion (Day 0) will occur as follows: * Fludarabine 30 mg/m2 per day IV for days 5, 4, 3 * Cyclophosphamide 500 mg/m2 per day IV for days 5, 4, 3 Autologous CD22-CAR T cells will be administered in 3 escalating doses (Dose Level 1, 2, and 3) to determine MTD/RP2D. Dose1: 1 x 10^6 cells/kg (± 20%) Dose2: 3 x 10^6 cells/kg (± 20%) Dose3: 1 x 10^7 cells/kg (± 20%) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (45 listed)
- Disease Status
- Subjects with transformed FL, MZL, or CLL/SLL who HAVE NOT received chemotherapy prior to transformation:
- oMust have received an anthracycline regimen and an anti CD20 monoclonal antibody (unless documented CD20-negative) and be refractory or relapsed after second line of DLBCL treatment. Subjects with a partial response to second line therapy must be ineligible for autologous transplant.
- •Subjects with transformed FL, MZL, or CLL/SLL who HAVE received anthracycline-containing chemotherapy prior to transformation: oMust have progressed, had SD or recurred with transformed disease after initial treatment for DLBCL.
- Measureable Disease
Key exclusion criteria (17 listed)
- Recurrent or refractory ALL limited to isolated testicular disease.
- Hyperleukocytosis (≥ 50,000 blasts/μL) or rapidly progressive disease that in the estimation of the investigator and sponsor would compromise ability to complete study therapy.
- History of other malignancy, unless disease free for at least 3 years. At the discretion of the Principal Investigator, subjects in remission for 1-2 years prior to enrollment may be deemed eligible after considering the nature of other malignancy, likelihood of recurrence during one year following CAR therapy, and impact of prior treatment on risk of CD22-CAR T cells. Subjects in remission <1 year are not eligible.
- Presence of active fungal, bacterial, viral, or other infection requiring intravenous antimicrobials. Simple UTI and uncomplicated bacterial pharyngitis are permitted if responding to active treatment.
- No knowledge of:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FludarabineFludarabine 30 mg/m2 | Drug | R/R ALL, R/R aggressive B-cell NHL |
| CyclophosphamideCyclophosphamide 500 mg/m2 | Drug | R/R ALL, R/R aggressive B-cell NHL |
| CD22 CARAutologous T cells transduced with lentiviral vector (CD22.BB.Z) Chimeric Antigen Receptor (CD22 CAR). Autologous CD22 CAR T cells will be administered intravenously at Dose Level 1 in subjects with ALL. Autologous CD22-CAR T cells will be administered in 3 escalating doses (Dose Level 1, 2, and 3) in subjects with aggressive B-cell NHL to determine MTD/RP2D | Drug | R/R ALL, R/R aggressive B-cell NHL |
Primary outcome
Rate of Successful Manufacture of CD22 CAR T Cells
Time frame: 7-11 days from start of manufacturing
The percentage of apheresis samples (fresh or frozen) that are successfully processed and expanded to manufacture CD22 CAR T cells will be determined for each dose cohort.
Incidence of Dose Limiting Toxicities (DLTs) in Subjects With Aggressive B-cell NHL
Time frame: 28 days after infusion
Incidence and severity of dose limiting toxicities (DLTs) following chemotherapy preparative regimen and infusion of CD22 CAR T cells, as recorded and graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, at each dose level tested in subjects with aggressive B-cell NHL
Safety Evaluation of CD22-CAR T Cells in Subjects With ALL
Time frame: 28 days after infusion
Incidence and severity of dose limiting toxicities (DLTs) following chemotherapy preparative regimen and infusion of CD22 CAR T cells, as recorded and graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, at each dose level tested in subjects with ALL
2 secondary outcomes
Clinical Activity of CD22-CAR T Cells in Adults With Relapsed/Refractory CD22-expressing B-cell ALL at Target Dose
Time frame: 28 days after infusion
Clinical Activity of CD22-CAR T Cells in Adults With Relapsed/Refractory Aggressive B-cell NHL at MTD/RP2D
Time frame: 3 months after infusion
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38996463Frank MJ, Baird JH, Kramer AM, Srinagesh HK, Patel S, Brown AK, Oak JS, Younes SF, Natkunam Y, Hamilton MP, Su YJ, Agarwal N, Chinnasamy H, Egeler E, Mavroukakis S, Feldman SA, Sahaf B, Mackall CL, Muffly L, Miklos DB; CARdinal-22 Investigator group. CD22-directed CAR T-cell therapy for large B-cell lymphomas progressing after CD19-directed CAR T-cell therapy: a dose-finding phase 1 study. Lancet. 2024 Jul 27;404(10450):353-363. doi: 10.1016/S0140-6736(24)00746-3. Epub 2024 Jul 9.
- Derived from this study: PubMed 33512414Baird JH, Frank MJ, Craig J, Patel S, Spiegel JY, Sahaf B, Oak JS, Younes SF, Ozawa MG, Yang E, Natkunam Y, Tamaresis J, Ehlinger Z, Reynolds WD, Arai S, Johnston L, Lowsky R, Meyer E, Negrin RS, Rezvani AR, Shiraz P, Sidana S, Weng WK, Davis KL, Ramakrishna S, Schultz L, Mullins C, Jacob A, Kirsch I, Feldman SA, Mackall CL, Miklos DB, Muffly L. CD22-directed CAR T-cell therapy induces complete remissions in CD19-directed CAR-refractory large B-cell lymphoma. Blood. 2021 Apr 29;137(17):2321-2325. doi: 10.1182/blood.2020009432.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Matthew Frank, MD, PhD principal investigator
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Fludarabine, Cyclophosphamide and CD22 CAR in people with B-ALL and B-cell Non Hodgkin Lymphoma, run by Matthew Frank at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 45 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Mar 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of Successful Manufacture of CD22 CAR T Cells (time frame: 7-11 days from start of manufacturing). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04088890, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2026.